Endocrinology

• the pituitary gland is attached by a stalk to the hypothalamus within the brain - and can be separated into the front (anterior) and back (posterior)
• cell types within the anterior pituitary include:

  • gonadotrophs
  • lactotrophs
  • corticotrophs
  • somatotrophs
  • thyrotrophs
• gonadotrophs produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to target gonads to produce both oestrogens and androgens
• lactotrophs target breast tissue and produce prolactin (PRL)
• corticotrophs produce adrenocorticotrophic hormone (ACTH) which targets the adrenal cortex to produce cortisol
• somatotrophs target the liver (IGF) and produce growth hormone (GH)
• thyrotrophs produce thyroid stimulating hormone (TSH) which targets thyroid tissue to produce thyroxine
• the anterior pituitary is controlled by hormones released from the hypothalamus
• most hypothalamic releasing factors are peptide hormones that stimulate the anterior pituitary gland for example thyrotrophin releasing hormone and corticotrophin-releasing hormone
• dopamine inhibits lactotrophs and somatostatin suppresses growth hormone
• thyratrophin releasing hormone stimulates teh release of thyroid stimulating hormone from the pituitary targeting the thyroid gland to release thyroid hormones
• corticotrophin-releasing hormones (CRH) stimulate the release of ACTH from the anterior pituitary to target the adrenal cortex to produce glucocorticoids
• gonadotrophin releashing hormones stimulate both FSH and LH to act upon the ovaries and testes to release inhibin, oestrogens, progestins and androgens
• menstrual irregularity among women can be due to a disturbance at the hypothalamus affecting the ovaries
• a pituitary tumour secreting excess ACTH can cause the over or under secretion of pituitary hormones
• the under or oversecretion within the endocrine gland can be due to thyroid failure (despite plenty of TSH) and is a problem with the thyroid, not the hypothalamus
• end-organ resistance can occur when there is a lack of receptor cells in the target organ (specifically for testosterone)
• low hormone concentrations in blood need very sensitive tests such as sensitive immunoassays, (IMAs) using monoclonal antibodies as there are better labels
• there is a lot of structural similarity between hormones:

  • steroid hormones have the same backbone
  • LH and HCG have the same alpha subunit (peptide hormones are often dimeric protein hormones)
• two site (sandwich) IMAs improve specificity for protein hormone assays
• many hormones circulate bound to protein as unbound "free" hormones are biologically active and hydrophobic, particularly steroid hormones. labels can therefore be designed to only equilibrate with free hormones
• patient's own antibodies can interact with the immunoassay antibodies giving false results
• there is biological variation in the release of hormones (pulsatility from pituitary, diurnal rhythms, stress increases cortisol and monthly cycles all need to be taken into account) so a single basal blood sample may give limited or misleading information
• dynamic function tests assist with the diagnosis of an endocrine problem as they test the whole or part of the hypothalamic-pituitary-target gland axis in a controlled way
• dynamic function tests are used:

  • if basal tests alone cannot rule for a diagnosis
  • check for residual gland function - see if there is any functioning tissue left
  • check if the secretion of hormones can be controlled or if it's autonomous (not responding to normal control methods)
• stimulation tests are when trophic (pituitary) or releasing hormones (hypothalamus) are given or a stress test is performed in cases of suspected hormone deficiency within the endocrine axis
• suppression tests use target hormones or synthetic target hormone analogue in cases of suspected hormone excess to check where on the endocrine axis the problem lies
• pituitary stimulation tests use releasing hormones whilst target gland stimulation tests use trophic hormones or their synthetic analogue
• some axes can be stimulated by biochemical or physiological stress such as the insulin hypoglycaemia stress test
• growth hormone is an anabolic hormone and affects the muscle liver and adipose tissue - and it can have insulin-like and anti-insulin effects
• growth hormones affect on muscle tissue is to increase amino acid uptake and protein synthesis, but decrease glucose uptake - leading to increased muscle mass overall
• growth hormones affect on the liver is an increase of protein synthesis, RNA synthesis, gluconeogenesis, and somatomedin production (leading to the release of somatomedins IGF-1 and IGF-2 or insulin-like growth factors)
• growth hormones affect on adipose tissue is a decrease in glucose uptake and an increase in lipolysis - causing an overall decreased adiposity
• indirect actions of growth hormone is the release of somatomedins

  • IGF-1 which affects chondrocytes of bone and increases collagen and protein synthesis, and cell proliferation causing an overall increased linear growth
  • IGF-2 affect many organs and tissues to increase protein, DNA, and RNA synthesis, cell size and number causing an overall increased tissue growth and organ size
• stimulators of GH include stress, exercise, hypoglycaemia, seep sleep, arginine and ghrelin (gut hormone)
• inhibitors of GH include hyperglycaemia somatostatin and REM sleep
• GH secretion is controlled through negative feedback loops with insulin-like growth factor 2
• short stature in children can be due to in probability order

  1. parental height
  2. inherited diseases
  3. poor nutrition/chronic illness
  4. emotional deprivation
  5. endocrine disorder
• short stature in children will be investigated by:

  • hight velocity(tanner growth chart for reference)
  • bone age (radiology of wrist and hand)
  • diabetes
  • thyroid/adrenal/gonadal disorder
  • GH deficiency (very rare)
• GH deficiency is very hard to prove as the size of the pulses vary throughout the night - and due to its pulsatile release a basal GH test is of limited value